Dopamine Agonists Pharmacology!

Dopamine Agonists Pharmacology

Dopamine agonists are used in the treatment of Parkinson’s disease and restless legs syndrome. Here, in this review of dopamine agonists pharmacology – we discuss these drugs in the context of Parkinson’s disease, fleshing out their mechanism of action, side effects and drug interactions.

Parkinson’s disease is named after the English physician, James Parkinson, who, in 1817, first described an account of this neurodegenerative disorder.

Symptoms of Parkinson’s disease include:

• Shakiness
• Rigidity
• Hypokinesia, or decreased bodily movement
• Gait abnormalities
• Dementia, in advanced stages of the disease

Other symptoms include depression, anxiety, insomnia, sensory and emotional problems.

Motor symptoms are collectively referred to as “parkinsonism” or “parkinsonian syndrome”; symptoms that derive from the death of cells in the substantia nigra of the midbrain.

The cause of cell death is not fully understood, but the collection of Lewy bodies (abnormal collections of protein) within neurons is believed to play a significant role. This results in dopamine deprivation in affected parts of the brain.

Worldwide, Parkinson’s disease affects up to 6 million people (as of 2015) and, in that year, resulted in almost 120,000 deaths. It is more likely to be found in males, as well as in persons with a family history of the condition. From the point of diagnosis, the average life expectancy is between 8 and 15 years.

While there is no cure, treatment is available. Dopamine agonists are one of the primary treatment options for the condition.

Indications

Of course, dopamine agonists are not the only source of drug treatment for Parkinson’s disease. Other medicines – such as levodopa and COMT inhibitors – are also widely used.

Dopamine agonists used to treat Parkinson’s disease include:

• Ropinirole
• Pramipexole
• Cabergoline
• Rotigotine
• Bromocriptine
• Apomorphine

As well as treating Parkinson’s disease, many of these drugs are also used to treat restless legs syndrome (RLS).

Cabergoline is more often used to treat prolactinomas, where there is too much prolactin in the blood. Similarly, bromocriptine is also used for this purpose, as well as acromegaly.

Mechanism of Action

Parkinson’s disease is in part caused by dopamine deficiency in the nigrostriatal pathway.

Without dopamine signals, the basal ganglia can no longer regulate motor movements, meaning motor function becomes impaired. Replenishing dopamine stores attenuates the severity of symptoms that patients experience.

Dopamine agonists are relatively selective for D₂ receptors and, through this agonism, it increases dopamine levels in the nigrostriatal pathway. These medicines also have activity at other dopamine receptor types.

For example – pramipexole has partial/full agonist activity at D₂, D₃ and D₄ receptors.

Side Effects

Side effects with dopamine receptor agonists include:

• Nausea
• Drowsiness
• Dizziness
• Confusion
• Hallucinations
• Sleep disturbances
• Hypotension
• Muscle weakness

Apormorphine is a highly emetogenic drug. For this reason, it is routinely given alongside an antiemetic.

Agonism at D₃ receptors – of which pramipexole and ropinirole are known – is known to produce unusual effects such as compulsive gambling, hypersexuality and overeating.

Many patients on dopamine agonists also experience peripheral edema, constipation and fatigue.

Clinical Pharmacology

When we talk about the clinical pharmacology of dopamine agonists, we need to think about the following factors:

• Caution is warranted in elderly patients or in those with established psychiatric disease due to the twin risks of confusion and hallucinations.
• Dopamine agonists cause hypotension – sometimes severe, and this must be factored into consideration in patients with cardiovascular disease.
• Dopamine agonists should be avoided with antipsychotic drugs or dopamine antagonist medicines, such as metoclopramide, where dopamine effects are cancelled out.
• Due to its highly emetogenic powers, apomorphine is typically administered alongside an antiemetic drug. Bromocriptine is also highly emetogenic, but not to the same level as apomorphine.
• Generally, dopamine agonists are used in the early stages of Parkinson’s disease and that other medicines, such as levodopa, are reserved as add-on treatment in later stages.
• Dopamine agonist therapy should never be abruptly stopped due to the risk of neuroleptic malignant syndrome (NMS). In addition, patient symptoms are likely to worsen very soon afterward.
• Patients may be unable to take oral formulations. Transdermal patches may then be used. For example – rotigotine is only available as a transdermal patch.

Dopamine agonists continue to play an important role in the treatment of Parkinson’s disease; medicines that restore dopamine activity in the nigrostriatal pathway, thereby reducing patient symptoms. They play a small role within a broader clinical approach that manages the many facets of this complex neurodegenerative disease.

That concludes our review of dopamine agonists pharmacology! Check back to our PharmaFactz blog soon for more exclusive content to help you master the science of drugs and medicines.